Dr. Tiffany Carson is an applied epidemiologist with a background in studying health disparities of black and white women. Dr. Carson's early work focused on behaviors related to diet, physical activity, obesity and related health outcomes. Recently, Dr. Carson has focused on applying her research efforts to better understand cancer disparities of black and white women. Dr. Carson's overarching career goal is to become an independently funded investigator and develop evidence-based bio-behavioral interventions to reduce cancer health disparities. To that end, this application proposes a rigorous research project and training plan focused on investigating the microbiota as a novel potential contributor to colorectal cancer (CRC) disparities between black and white women. CRC is the 2nd leading cause of cancer death in the United States accounting for 9% of cancer deaths. Known risk factors for CRC include increasing age, male sex, family history, inflammatory bowel disease, type 2 diabetes, alcohol consumption, smoking, physical inactivity, high consumption of red and processed meats and high fat diet, and obesity. Among women, even after accounting for differences in the distribution of risk factors, black women remain at 48% greater risk for CRC than white women. There is a growing body of research suggesting that the influence of diet on CRC risk is mediated through the microbiota and that microbial perturbations caused by diet, lifestyle, and antibiotics can lead to increased risk for CRC and other chronic diseases. Stress is one factor that has been shown to lead to alterations in the microbiota. Our research has shown that black women report moderate to high stress levels and additional published literature indicates that black women report higher stress levels than their white counterparts. These observations have lead to our hypothesis that a greater proportion of black women have a perturbed microbiota as a result of higher stress levels compared to white women, putting black women at greater risk for developing CRC. In the present proposal, we plan to explore this hypothesis employing a case control study design comparing the following groups: 1) black and white women with incident CRC from the Kirklin Clinic at UAB and 2) age-matched cancer-free black and white female community controls. Specifically, we will first characterize the oral and gut microbiota of black and white women with CRC and compare by race with particular focus on microbes known to be either positively or negatively associated with CRC. Because all cases will have CRC, we hypothesize that there will be no significant racial differences in the microbiota or other known risk factors for CRC such as diet. In contrast, when we repeat this experiment in cancer-free black and white female community controls, we expect to observe racial differences in the microbiota, with black women having less health-promoting bacteria and more pathogenic bacteria than white women, which would put black women at increased risk for CRC. We anticipate that a greater proportion of black females in the control group will have microbiota that resembles the microbiota of participants with CRC. Additionally, if our hypothesis is supported, psychological stress with be inversely associated with health-promoting bacteria and positively associated with pathogenic bacteria. Our findings will provide insight into how lifestyle factors that have not been fully explored to date such as stress may be associated with risk for CRC as a result of how stress perturbs the microbiota. If we determine that stress contributes to CRC risk via microbial perturbations, future bio-behavioral interventions that incorporate stress management and dietary/supplemental recommendations to promote mucosal health, and therefore reduce CRC risk, can be developed and implemented which could lead to diminished health care costs related to diagnosis and treatment and reduce CRC disparities between black and white women. In addition to providing valuable data, the proposed research project will also provide the opportunity for the additional training needed for Dr. Carson's development as an independently funded bio-behavioral cancer disparities researcher. Dr. Carson will engage in an intensive, structured training experience to develop expertise by completing the following: 1) Training in the recruitment of racially diverse clinical and community populations for bio-specimen and bio-banking research, 2) Obtaining hands-on and didactic training in bioinformatics techniques, and 3) Improving professional skills such as team science, networking, grant writing, mentoring, and high-impact publications. Under the guidance of an esteemed panel of mentors and collaborators and the high quality research and training environment that the University of Alabama at Birmingham offers, Dr. Carson's research and training experiences will make a significant contribution to the scientific community and Dr. Carson's overall career development.